title: Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection.
abstract: OBJECTIVE
  T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) represents a novel mechanism of T-cell dysfunction in chronic viral diseases. However, the role of Tim-3 in the pathogenesis of chronic hepatitis B (CHB) is not well understood. We investigated Tim-3 expression on peripheral T cell subsets and analyzed the relationship between Tim-3 expression and disease progression in HBV infection.
  
  
  METHODS
  peripheral blood samples were obtained from CHB patients (n = 40), including 23 patients with moderate CHB [MCHB] and 17 with severe CHB [SCHB]. Control samples were obtained from nine acute hepatitis B patients (AHB) and 26 age-matched healthy subjects. The expression of Tim-3 on T cells was determined by flow cytometry.
  
  
  RESULTS
  Tim-3 expression was elevated on peripheral CD4+ and CD8+ T cells from AHB and CHB patients compared to those from healthy controls. The percentage of Tim-3+ T cells was further increased in SCHB patients relative to MCHB patients and showed a positive correlation with conventional markers for liver injury (alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB) and international normalized ratio (INR) level). The frequency of Tim-3-expressing T cells was negatively correlated with T-bet mRNA expression and plasma interferon-gamma (INF-gamma) levels. Further, Tim-3 expression on CD4+ or CD8+ T cells was reduced in CHB patients with disease remission after antiviral treatment and in AHB patients during the convalescence phase.
  
  
  CONCLUSIONS
  Our results suggest that over-expression of Tim-3 is involved in disease progression of CHB and that Tim-3 may participate in skewing of Th1/Tc1 response, which contributes to persistency of HBV infection.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D007371:Interferon-gamma